U.S. patent application number 13/888252 was filed with the patent office on 2013-09-19 for analytical devices with integrated desiccant.
This patent application is currently assigned to QUIDEL CORPORATION. The applicant listed for this patent is QUIDEL CORPORATION. Invention is credited to Sarah Dennison, Kevin J. Kirby.
Application Number | 20130244315 13/888252 |
Document ID | / |
Family ID | 39586961 |
Filed Date | 2013-09-19 |
United States Patent
Application |
20130244315 |
Kind Code |
A1 |
Kirby; Kevin J. ; et
al. |
September 19, 2013 |
ANALYTICAL DEVICES WITH INTEGRATED DESICCANT
Abstract
An analytical device for performing an assay to determine the
presence or approximate quantity of at least one analyte in a
liquid sample is described. The device is manufactured to include
an integrated desiccant within at least a test strip of the device.
Addition of an integrated desiccant within the device improves
signal to noise ratio, eases the manufacturing process, and saves
in cost of production of the device.
Inventors: |
Kirby; Kevin J.; (Valley
Center, CA) ; Dennison; Sarah; (San Diego,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
QUIDEL CORPORATION |
San Diego |
CA |
US |
|
|
Assignee: |
QUIDEL CORPORATION
San Diego
CA
|
Family ID: |
39586961 |
Appl. No.: |
13/888252 |
Filed: |
May 6, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12148344 |
Apr 17, 2008 |
8435461 |
|
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13888252 |
|
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|
60925592 |
Apr 20, 2007 |
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Current U.S.
Class: |
435/287.2 |
Current CPC
Class: |
B01L 2300/0887 20130101;
B01L 2300/105 20130101; G01N 33/56983 20130101; B01L 3/5023
20130101; G01N 33/54393 20130101; B01L 2300/0825 20130101; G01N
33/56938 20130101 |
Class at
Publication: |
435/287.2 |
International
Class: |
G01N 33/569 20060101
G01N033/569 |
Claims
1. A lateral flow immunoassay device for detection of an analyte in
a biological sample, comprising: an analytical test strip
comprising a support member, a plurality of porous pads in fluid
communication, said plurality of porous pads in contact with the
support member and including, in sequence, a sample receiving pad,
a label pad containing mobile tag reagents, a test pad containing
immobilized binding reagents, and an absorbent pad which serves as
a sink zone, and a desiccant portion, comprising a film or membrane
having desiccant dispersed therein, which is laminated to the
analytical test strip, such that said desiccant is disposed
adjacent the absorbent pad, wherein said desiccant portion remains
integral with the analytical test strip during use thereof.
2. The device of claim 1, wherein the desiccant portion is not in
fluid communication with the plurality of porous pads.
3. The device of claim 1, wherein the desiccant portion comprises a
material selected from the group consisting of molecular sieves and
silica gel.
4. The device of claim 1, wherein the analytical test strip is in
the form of a dipstick.
5. The device of claim 1, wherein said mobile tag reagents and
immobilized reagents are capable of binding an influenza A
analyte.
6. The device of claim 5, comprising two test lines within said
test pad, containing immobilized reagents capable of binding
influenza A and influenza B analytes, respectively.
7. The device of claim 1, wherein said mobile tag reagents and
immobilized reagents are capable of binding a Streptococcus
pyogenes analyte.
8. The device of claim 1, wherein the desiccant is integrated into
the device by (i) providing a desiccant-loaded film or membrane;
and (ii) laminating said desiccant-loaded film or membrane to the
test strip.
9. The device of claim 1, wherein the desiccant portion is
positioned above at least the absorbent pad.
10. The device of claim 1, wherein the desiccant portion is
positioned below at least the absorbent pad.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The application is a continuation of U.S. application Ser.
No. 12/148,344, filed Apr. 17, 2008, which claims the benefit of
U.S. Provisional Application No. 60/925,592, filed Apr. 20, 2007,
each of which are incorporated herein by reference in its
entirety.
TECHNICAL FIELD
[0002] The subject matter described herein relates to devices for
detecting the presence or approximate quantity of a chemical or
biological substance (an analyte) in a biological sample. More
particularly, the subject matter relates to immunoassay devices
comprising a desiccant integrated into a portion of the device, and
preferably into a portion capable of analyte detection.
BACKGROUND
[0003] Devices for the rapid qualitative and/or quantitative
detection of analytes in a liquid sample often involve a sandwich
type assay, frequently immunoassay, wherein certain reagents
necessary for performance of the assay are located within the
device. The device reagents are typically disposed within in the
device in a dry form. During storage of the device prior to use, it
is desirable to prevent adsorption and/or absorption of moisture
onto the dry reagents, in particular for reagent that may be
inactivated or desensitized by water molecules. Chemical drying
agents, e.g., desiccants, for absorbing/adsorbing moisture are
known in the art, and are typically included, for example, as a
separate sachet in the package for the device or in a separate
compartment of the device. There remains a need, however, to reduce
or prevent moisture uptake by reagents and other components in a
diagnostic assay device, where the desiccant is incorporated in
such a way that it cannot contaminate the device reagents nor
interfere with performance of the device. It is further desirable
that such desiccant be incorporated in a manner that can improve
manufacturing efficiencies, for example by decreasing manufacturing
time and/or costs.
BRIEF SUMMARY
[0004] The following aspects of the present invention and
embodiments thereof described and illustrated below are meant to be
exemplary and illustrative, not limiting in scope.
[0005] In one aspect, analytical devices for performing an assay to
determine the presence or approximate quantity of at least one
analyte in a liquid sample are described. The devices have
improvedstability and/or manufacturability due to integration of a
desiccant into one or more distinct regions within the device.
[0006] In another aspect, an analytical device for detecting the
presence or approximate amount of an analyte in a sample is
provided. The device comprises an analytical test strip and a
desiccant material integrated into the analytical test strip.
[0007] In one embodiment, the desiccant is a material selected from
molecular sieves and silica gels.
[0008] In certain other embodiments, the desiccant is integrated
into the analytical test strip by laminating a desiccant-loaded
sheet or film to the test strip or by securing a desiccant to the
test strip by an adhesive.
[0009] In another embodiment, the desiccant is integrated into the
test strip by a mechanical means.
[0010] The analytical device, in one embodiment, comprises an
analytical device in the form of a dipstick.
[0011] Other objects, features and advantages of the compositions
and methods of the present invention will be apparent from the
following detailed description. It should be understood, however,
that the detailed description and the specific examples provided
herein, while indicating specific embodiments, are given by way of
illustration only, since various changes and modifications within
the spirit and scope of the invention will be apparent to those
skilled in the art based upon the teachings in this detailed
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a view of an exemplary analytical device
containing an integrated desiccant.
[0013] FIGS. 2A-2B are graphs showing the percentage of devices
(fabricated either with (triangles) or without (squares) an
integrated desiccant) at each time point that produced a positive
test line (indicating presence of influenza A analyte), as a
function of time, in weeks or days, respectively, of storage of the
devices at 45.degree. C.
[0014] FIG. 3 is a graph showing the percentage of devices
(fabricated with (triangles) an without (squares) an integrated
desiccant) at each time point that produced a positive test line
(for detection of Strep A), as a function of time, in weeks, of
storage of the devices at 45.degree. C.
DETAILED DESCRIPTION
I. ANALYTICAL DEVICE
[0015] As used in this specification and the appended claims, the
singular forms "a," "an" and "the" include plural referents unless
the context clearly dictates otherwise.
[0016] In one aspect, an analytical device having a desiccant as an
integrated component of the device is provided. In a preferred
embodiment, the desiccant is an integral component of one or more
regions of the test strip in the analytical device. The analytical
device is preferably one for use in determining the presence or
approximate quantity of one or more analytes in a fluid sample. As
will be illustrated herein, a desiccant integrated into one or more
regions of the analytical test strip region of the device improves
manufacturability of the device. An integrated desiccant also
reduces the likelihood that the assay reagents within the device
will become contaminated, by moisture or by a non-integrated, loose
desiccant, during storage, which contamination could impair the
functionality of the device. An integrated desiccant can also be
more cost efficient in product production.
A. Exemplary Assay Devices
[0017] A variety of analytical diagnostic devices include a test
region or test strip that contains reagents for detection of a
sample analyte. Such devices have a variety of configurations and
geometries, and a desiccant integrated into the test region of any
of these analytical devices is contemplated. For purposes of
illustrating a device having an integrated desiccant, an exemplary
device is shown in FIG. 1. This device, and other devices, are
described, for example, in U.S. Pat. Nos. 6,656,744; 6,924,153, and
in U.S. Publication No. 2005/0227371, which are incorporated by
reference herein. In brief, the device in FIG. 1 is known in the
art as a `dipstick` device and is capable of producing a relevant
signal dependent upon the presence of a specific analyte in a
liquid sample. Device 100 is comprised of a sample receiving pad or
portion (which may optionally comprise a neutralization pad) 110, a
label pad 120, a porous portion 130,comprising at least one test
line 132, and, preferably, control line 134, an absorbent pad 140,
and a desiccant portion 150, wherein the various portions of the
device are secured, in fluid communication with one another, to a
support member 160; provided however, that desiccant portion 150
may be adjacent but not in contact with (and thus not in fluid
communication with) support 160. The support member 160 is
typically fabricated from a non-porous rigid or semi-rigid
material. Collectively, the support with the various portions
secured thereto is referred to herein as a "test strip" or an
"analytical test strip."
[0018] Sample receiving pad 110, label pad 120, and porous portion
130 can be directly touching or abutting the adjacent member
thereto or can be in an overlapping arrangement with an adjacent
member. For example, referring to FIG. 1, porous portion 130 and
absorbent pad 140 may be assembled in overlapping relationship,
provided however, they are arranged so as to not interfere with
test line 132 or control line 134.
[0019] In FIG. 1, desiccant portion 150 is shown as a discrete, but
integral, region at a distal end of the test strip. In a preferred
embodiment, desiccant 150 is adjacent to and in contact with or
nearly in contact with absorbent pad 140. Placing desiccant in this
position is unrelated to functionality of either the test strip or
desiccant but is selected for aesthetic reasons. It is
contemplated, however, that a desiccant may be disposed at one or
more of various locations along the test strip of the device. In a
preferred embodiment, as shown in FIG. 1, the desiccant is an
integral part of the test strip, but is not in direct contact with
the absorbent pad. It is contemplated, however, that the desiccant
can be included in the test strip so as to directly touch adjacent
pads or portions, such as absorbent pad 140, or to overlap with one
or more pads or portions of the test strip, without interfering
with operation of the test strip. For example, and in one
embodiment, desiccant portion 150 extends the length of the test
strip of the device, disposed between support 160 and the various
portions, where the extension of the desiccant can be continuous or
non-continuous. When non-continuous, the desiccant portion is in
contact with some, but not all portions of the test strip. In some
embodiments, the desiccant portion may function as the support.
[0020] In a preferred embodiment, as shown in FIG. 1, sample
receiving pad 110 is disposed at a proximal end of device 100,
where a liquid sample is brought into contact with the device. Upon
contact with sample receiving pad 100, the sample flows through the
test strip of the device in the direction indicated by arrow 165,
through the label pad 120 and porous portion 130 towards the distal
end of the device. Test line 132 comprises an irreversibly
immobilized reagent capable of interaction with analyte. The porous
portion can optionally include a control zone 134 that comprises an
irreversibly immobilized control reagent.
[0021] The opposing (or distal) end of device 100, comprises an
absorbent pad 140 which serves as a sink zone.
[0022] In use, a fluid sample, such as a solution comprising a
physiologic sample such as blood, serum, plasma, urine, saliva,
mucous, spinal fluid, nasal wash, nasal aspirate, or the like, is
introduced onto sample receiving pad 110 at the proximal end of the
device. The sample may be added directly to the device in the
original form as obtained from a subject, or may be treated, for
example by addition of a buffering, extraction and/or other
solution, prior to application to the device. Once added, the
sample flows along a primary flow path, defined by the pads and
portions, in the direction of arrow 165. In one embodiment, the
sample receiving pad is formed from a non-bibulous material, such
as the inert polyethylene material marketed as Porex.TM., or of a
material with moderate bibulous nature such as spun nylon, which
can be treated with an agent to confer non-bibulous characteristics
if desired. The absorbent pad is preferably formed from materials
that absorb and retain liquid and liquid components, including for
example, latex, and which tends to restrict or prevent the reverse
flow of components such as latex. By way of example, exemplary
absorbent pad materials may consist of polyester, cellulose blends,
nitrocellulose, and the like.
[0023] Porous portion 130 preferably is in fluid communication with
label pad 120, as is the case in device 100. The porous material in
porous portion 130 facilitates flow within the device by, for
example, by absorbing fluid from the label pad 120 into or onto the
porous portion. A "porous" material or component refers to a
material comprising pores through which liquid may flow. By way of
example, a porous material may be comprised of a network of
insoluble material that supports liquid flow by capillary force.
Typically, the pores within porous materials form randomly
oriented, tangled open spaces connected to each other and forming a
network of liquid-wicking ducts. Porous materials may be formed
from natural and/or synthetic materials, fibrous or particulate.
Porous materials suitable for use herein are well known to those of
skill in the art and include, for example and without limitation,
nitrocellulose-based materials, polymer-based materials, such as
porous polyethylene, acrylic-based materials, such as spun laced
acrylic, fibrous glass materials, paper materials and the like.
[0024] With continuing reference to use of device 100, when the
sample contacts the label pad, the tag(s) located therein are
mobilized. The tag(s) is (are) a component capable of binding an
analyte present in the sample to form a complex. When sample
contacts the label pad, the tag is released, for example by
hydration or solubilization, becoming mobile with the sample. As
sample and tag mix, they combine to form tagged analyte. Tags
include, for example, antigens, haptens, antibodies, ligands,
receptors, nucleic acid molecules, or chemical reactants. Tags may
be linked to a directly detectable label, such as a colored latex
particle, a light absorbing moiety, a chemiluminescent moiety or a
particle, or the tag may be linked to an indirectly detectable
label, such as an enzyme, for example including, without
limitation, a hydrolase, esterase (for example, alkaline
phosphatase) or oxidoreductase (for example, horseradish
peroxidase).
[0025] In certain preferred embodiments, the label pad is comprised
of a porous material, such as one of the materials described above.
In alternative embodiments, one or more portions of the device,
such as for example the sample receiving portion and/or label
portion, are comprised of non-porous material. A "non-porous"
material refers to a material through which insubstantial
quantities of fluid (for example, liquid) flow. Typically, a water
insoluble material is used as the non-porous material, and in
preferred embodiments, the material is inert and impermeable to
fluids used under normal assay conditions. Exemplary "non-porous"
materials include, without limitation, thermoform or thermoplastic
polymers (e.g. polystyrene, polyethylene, polycarbonate,
polypropylene, fluoropolymer, or polyester, or a combination),
glass, metals, ceramics or composite materials well known to those
skilled in art. A non-porous surface can also be made of any
material which is surface coated to render it impermeable to fluid.
For example, a porous material can be coated with a low protein
binding, non-water absorbing material such as a fluoropolymer
resin, exemplified by Teflon.TM., or a polyester film, exemplified
by Mylar.TM..
[0026] The sample, now comprising a tagged analyte if analyte is
present therein, then flows into contact with the test line 132
where tagged analyte is captured. The test line typically comprises
a binding reagent immobilized on or in a discrete region of the
test strip, which binding reagent is capable of binding or
otherwise interacting with and immobilizing the tagged analyte
complex. Those of skill in the art will recognize that an analyte
may be a component of the sample or a derivative or analogue of a
sample component or the like. An irreversibly immobilized reagent
refers to a reagent that is not appreciably solubilized or
displaced by the passage of liquid sample under the liquid flow
conditions applied in the routine or optimal operating conditions
for the device. The binding reagent located in the test line is
capable of binding or otherwise interacting with the analyte or a
component of the analyte complex to retain (immobilize) the analyte
or component. For example in a sandwich assay format, the
mobilizable tag may contain an antibody that is a first binding
partner of the target analyte and the test line may contain an
immobilized antibody that is a second binding partner of the
analyte (or analyte complex). Thus, at the test line, the analyte
is "sandwiched" between the two antibodies. In a competitive assay
system, the analyte displaces or competes with its analog or
derivative in the test line, wherein the analyte or its derivative
are labeled in the label pad upstream of the test line.
[0027] The sample continues to flow past the test line and,
optionally, into contact with a control zone and then into the
remaining porous material or other materials at the distal end of
the device, such as absorbent pad 140, that, at least in part, act
as a sink for the sample. The control zone is preferably located
downstream of the test line, particularly where the device is
designed for detection of a single analyte in a liquid sample.
Where more than one analyte is to be detected and thus more than
one test line is employed within the device, it may be preferable
to locate a control zone between two test lines. The control zone
may be designed to generate a signal that indicates that the liquid
sample has indeed flowed through the device past the test line, and
therefore, that the assay is working as designed. The control zone
generally will comprise an immobilized reagent ("immobilized
control reagent") that either is capable of generating a detectable
signal as a result of interaction with a component of the sample
or, more preferably, is capable of binding a control reagent
comprising a detectable moiety. Optionally, the control zone may
function as a "reference" zone to aid in determination of the
presence or approximate quantity of the analyte in the aqueous
sample or both control and reference zones may be employed in the
device. The control zone may also function as a negative or
positive control.
[0028] As described above, the test strip includes an integrated
desiccant, exemplified in device 100 by desiccant portion 150. The
desiccant portion of the device may be disposed in one or more
regions of the device. By way of example, a desiccant region or
layer can be adjacent, but not in direct contact with, an absorbent
pad, as shown in FIG. 1. Alternatively, the desiccant can be
directly adjacent and in physical contact with absorbent pad 140.
Alternatively, the desiccant can be in an overlapping arrangement
with a top or bottom surface of one or more pads, portions, or
regions of the test strip, preferably without interfering with the
test line(s) 132 or control line 134. In one embodiment, a
desiccant portion is disposed as an intervening layer between
support 160 and one or more of the pads, lines, or portions
supported on the support. In another embodiment, support 160
comprises desiccant.
[0029] As can be appreciated, the desiccant is an integral part of
the test strip, by virtue of its being in direct contact with one
or more regions (for example the support) of the test strip. The
desiccant, in a preferred embodiment, is integrated into the device
in the form of a film or membrane, for example, a polyurethane film
having desiccant dispersed therein. An example of a desiccant in
the form of a film or tape is described in U.S. Pat. Nos. 7,005,459
and 6,613,405, which are incorporated by reference herein, where a
desiccant is entrained in a polymer that is manufactured into a
film or tape. In this form, the desiccant provides a stable,
non-reactive, non-corrosive material that does not leave
particulates capable of interfering with performance of the device,
as can occur when a desiccant in loose form or in a sachet is
disposed in the housing or packaging of the device. The integrated
desiccant need not be sequestered from other parts of the device,
such as by placement away from certain portions of the device, by
use of a protective coating over the desiccant, or by packaging of
the desiccant within other materials to form a sachet or film that
is removed prior to use of the device. That is, the integrated
desiccant material may be in contact with the sample, need not be
removed prior to use, and does not interfere with performance of
the device.
[0030] The device can optionally include one or more conditioning
reagent zone(s) that comprise(s) sample treatment reagents to
improve the performance of the assay, including, e.g., changing the
pH, salt concentration or metal ion concentration, adding or
removing inorganic or organic components or detergents, blocking
non-specific interactions or removal/filtering of large and/or
interfering components of the sample, such as for example, red
blood cells from whole blood samples. Conditioning zone(s) may be
included at or near the point of sample application and/or on/in
either or both porous or non-porous material.
B. Desiccants
[0031] Desiccants suitable for integration into the test strip of
an analytical device, like that described above, can be selected
from a wide variety of materials, and in a preferred embodiment is
a material capable of extracting and retaining moisture from an
ambient environment having a humidity of at least up to about 5%
humidity, more preferably of up to about 10-12% humidity. Desiccant
materials capable of moisture absorption by a physical absorption
process are preferred, however, materials that combine with water
to form a hydrate or that react with water to form a new compound
within which the water is combined may also be used.
[0032] Desiccants that absorb by physical absorption of moisture
include molecular sieves, silica gels, clays (e.g., montmorillimite
clay), certain synthetic polymers, and starches. In one embodiment,
the molecular sieve pore sizes in the desiccant are between about
3-15 Angstroms.
[0033] Examples of desiccants include, but are not limited to,
alumina, bauxite, anhydrous calcium sulfate, water-absorbing clays,
silica gel, zeolite and any of the other moisture-absorbing
materials known to the art. Other exemplary desiccants are
described in detail in U.S. Patent Nos. 5,911,937, 6,214,255,
7,005,459, 6,613,405, and 6,130,263, which are incorporated by
reference herein.
[0034] It will be appreciated that various moisture sensitive
indicators, e.g. cobalt chloride, which change color to indicate
extent of moisture uptake by the desiccant, can be optionally
included, and some commercial desiccants include such an indicator
compounded with the desiccant.
[0035] The stability, or useful lifetime, of the reagents within an
analytical device is a function, at least in part, of the extent of
exposure to humidity during storage or prior to use. The present
device, having an integrated desiccant, provides a shelf-life
adequate for commercial purposes and with expected improved shelf
life as compared to currently available devices. Shelf-life can be
evidenced by, for example, the test reagents, such as an antibody,
remaining capable of interaction with an analyte, for the duration
of the shelf-life period.
C. Analytical Device with Integrated Desiccant
[0036] A desiccant can be integrated into the test strip of an
analytical diagnostic device in a variety of configurations and by
a variety of attachment techniques. In a preferred embodiment, the
desiccant in integrated into the test strip in the form of a film.
For example, a desiccant incorporated into an elastomeric polymer
can be coated onto a support or a release paper to form a flexible
desiccant-loaded polymer film. The film can be coated directly onto
one or more regions of the test strip, or can be secured to one or
more regions of the test strip by an attachment technique.
[0037] In one embodiment, a desiccant is secured to one or more
regions of a test strip using an adhesive. Examples of adhesives
include, but are not limited to paste, putty, rubber cement,
mucilage, birdlime, sealant, epoxy, and stickum. In other
embodiments, the desiccant is integrated into the device by
lamination of a desiccant or desiccant-containing material to one
or more regions of a test strip. In another embodiment, the
desiccant is integrated into the device by a mechanical means.
Examples of a mechanical means include, but are not limited to
stapled, riveted, tethered, pinned, strapped, leashed, cinched,
wrapped, laced, hemmed, fused, bound, tied, fastened, soldered,
merged, welded, and sealed.
[0038] In a preferred embodiment, the diagnostic assay device
described herein is primarily employed in assaying either antigens
or antibodies through the formation of an immune complex. However,
it will be appreciated that the device need not be limited to an
assay of these molecules. The device merely requires a first
molecule that recognizes and binds a second molecule. The first
molecule can be conveniently termed a ligand-recognition molecule,
and the latter a ligand. While antibody and antigen are preferred
aspects of a ligand-recognition molecule and ligand respectively
the device can be used with a variety of ligands and
ligand-recognition molecules. For example, hormone receptor
molecules are a type of ligand recognition molecule and can be
attached to the solid matrix material, and used to assay for the
corresponding hormone ligand. Alternatively, a hormone could be
bound to the matrix material and used to assay for hormone
receptors. It will be apparent to those skilled in the art that
there are many such combinations of ligand-recognition molecules
and ligands suitably employable in the present immunodiagnostic
device.
[0039] Devices containing an integrated desiccant were prepared as
described in Examples 1 and 2, for detection of influenza A (with
influenza B test line included thereon) and Strep A. Devices
without an integrated desiccant were fabricated, to serve as a
comparative control. The devices were stored at 45.degree. C. and
tested weekly to evaluate the device ability to detect influenza or
Strep, applied to the device in a standard test solution. Results
for the devices for diagnosis of influenza are shown in FIGS. 2A-2B
and for diagnosis of Strep A in FIG. 3.
[0040] In FIGS. 2A-2B, the number of devices tested at each time
point that had a positive test line relative to the total number of
devices tested at each time point is shown. Devices with an
integrated desiccant (triangles) consistently exhibited a positive
test line, relative to the devices without an integrated desiccant
(squares), for detection of influenza A and B.
[0041] Devices for detection of Streptococcus pyogenes ("Strep A")
were prepared as described in Example 2, and the test results after
storage at 45.degree. C. are shown in FIG. 3. The number of devices
tested at each time point that had a positive test line upon
application of a test solution containing Strep A relative to the
total number of devices tested at each time point is shown. Devices
with an integrated desiccant (triangles) consistently exhibited a
positive test line, relative to the devices without an integrated
desiccant (squares), for detection of Strep A.
[0042] While the invention has been described in connection with a
preferred embodiment, it is not intended to limit the scope of the
invention to the particular form set forth, but on the contrary, it
is intended to cover such alternatives, modifications, and
equivalents as may be included within the spirit and scope of the
invention as defined by the appended claims.
II. EXAMPLES
[0043] The following examples are illustrative in nature and are in
no way intended to be limiting.
Example 1
Preparation of Analytical Devices Comprising An Integrated
Desiccant for Detection of Influenza
[0044] A dipstick test device for detection of influenza A and
influenza B was prepared as follows. A nitrocellulose membrane
(Millipore) was laminated to a Mylar-Polyvinylchloride (PVC)
backing. Two test lines for detection of influenza A and influenza
B, respectively, were applied to the nitrocellulose membrane by
spotting with a solution of anti-influenza A/nucleoprotein (NP) and
a solution of anti-influenza B/NP. A control line was applied to
the nitrocellulose membrane by spotting a solution of
streptavidin-bovine serum albumin (BSA) conjugate. The layer was
air dried for 5 minutes.
[0045] Solutions containing anti-influenza A nucleoprotein-coupled
latex particles and anti-influenza B nucleoprotein-coupled latex
particles and biotinylated BSA control beads were dispensed on an
acrylic fiber to form a label pad. The pad was allowed to dry for 5
minutes.
[0046] The label pad and a sample receiving pad were laminated by
hand to the Mylar-PVC, in a standard lateral flow test
configuration (see, for example, FIG. 1). A cellulose absorbent pad
was laminated adjacent to the nitrocellulose membranes containing
the test and control lines.
[0047] A desiccant film was then laminated onto the Mylar-PVC
adjacent to the absorbent pad in some of the devices. For
comparison, devices without the desiccant film were prepared.
[0048] Immediately after device construction and then weekly after
storage at 45.degree. C., a device was tested to evaluate its
ability to detect influenza A analyte in a standard test solution.
The test sample containing recombinant influenza A/NP was applied
to the receiving pad and the test lines were observed to determine
if the device was able to detect influenza A/NP. Results from
duplicate experiments are shown in FIGS. 2A-2B with FIG. 2A showing
data taken at various weekly time points over 16 weeks and FIG. 2B
showing data taken at various daily time points over about 350
days.
Example 2
Preparation of Analytical Devices Comprising An Integrated
Desiccant for Detection of Streptococcus pyogenes
[0049] A dipstick test device for detection of Streptococcus
pyogenes ("Strep A") was prepared as described in Example 1, except
a single test line was formed by spotting a solution of rabbit
Anti-Strep A antibody, and a control line was formed by spotting a
solution anti glucose oxidase. Strep A coupled test latex beads and
Glucose Oxidase control latex beads were applied to the acrylic
fiber to form the label pad.
[0050] Devices identical in all respect except for the presence or
absence of a desiccant film were tested immediately after device
construction and then weekly after storage at 45.degree. C. by
applying a test sample containing Strep A. Results are shown in
FIG. 3.
[0051] While a number of exemplary aspects and embodiments have
been discussed above, those of skill in the art will recognize
certain modifications, permutations, additions and sub-combinations
thereof. It is therefore intended that the following appended
claims and claims hereafter introduced are interpreted to include
all such modifications, permutations, additions and
sub-combinations as are within their true spirit and scope.
* * * * *